Eutrophication and warming have facilitated the proliferation of harmful cyanobacterial blooms in freshwater ecosystems. Consequently, understanding and predicting the dynamic responses of dominant cyanobacterial groups under global change represents a critical challenge in freshwater ecology. In this study, we analyzed cyanobacterial environmental DNA (eDNA) from 879 sites across 188 Chinese lakes and modeled the distribution of dominant genera along gradients of key environmental variables using hierarchical logistic regression to assess niche preferences and species responses. Results indicated that harmful cyanobacteria—including Planktothrix, Microcystis, Cylindrospermopsis, Nodosilinea, Dolichospermum, Sphaerospermopsis, Aphanizomenon, Pseudanabaena, and Planktothricoides—primarily dominated in China’s Eastern Plain (EP) and Yunnan-Guizhou Plateau (YG) regions. Cyanobacterial community structure was primarily influenced by temperature (Tem), followed by total phosphorus (TP) and total nitrogen (TN). Most harmful cyanobacterial taxa exhibited niche differentiation along temperature and nutrient gradients. While the majority were thermophilic (>25°C), some—such as Cylindrospermopsis, Aphanizomenon, and Pseudanabaena—thrived at lower temperatures (15–24°C). Nutrient specialization also varied: Microcystis and Planktothricoides were associated with high phosphorus (P) concentrations, whereas Pseudanabaena and Cylindrospermopsis dominated in relatively low-P environments. Despite being nitrogen-fixing genera, Cylindrospermopsis and Dolichospermum were abundant in high-nitrogen areas, whereas non-N2-fixing taxa (e.g., Microcystis, Planktothrix) prevailed in ammonium-rich (NH3-N) waters. The random forest models also indicated that harmful genera such as Microcystis and Dolichospermum exhibited increased dominance under the low-emission (SSP1-2.6) scenario, with further intensification under the high-emission (SSP5-8.5) scenario. These findings underscore the important implications for bloom mitigation under future climate regimes.